Project summary: Host-microbial interactions are a critical determinant of health. The intestinal mucosa provides serval distinct overlapping mechanisms that function together in concert to reduce the ability of pathogens to gain access to the body. These protective mechanisms are largely provided by specialized intestinal epithelial cells that can produce mucous and bactericidal antimicrobial peptides. While it has long been known that neurotransmitters control this process, it had been assumed that these originated from neurons. Recently we have identified a unique subset of B- and T-cells that produce the neurotransmitter acetylcholine, and that are specifically recruited during enteric bacterial infection. The overall goals of this project are to determine the role of these unique B- and T-cells and elucidate the mechanisms of protection that are elicited. This will be achieved by using neutralizing antibodies and conditional knockout mice to decipher the role of these cells during infection (SA1). Determining if these B- and T-cells are protective to the host by increasing mucous production and release will be assessed in SA2. The ability of these cells to induce expression of antimicrobial peptides will also be assessed in SA2. Together, these proposed studies will decipher the contribution of a unique immune cell population to mucosal host defense.